The sole specific aim of the training described in this proposal is to provide postdoctoral fellows with state-of-the-art research training in the basic biologic sciences which are relevant to unsolved problems in the fields of trauma and sepsis. Our primary goal is to train clinicians, usually surgeons, to reduce clinical problems in trauma and sepsis into their essential biological components -- the biological questions can then be addressed by sustained and imaginative laboratory investigation. By and large, these biological questions are so complex that coordinate and sophisticated approaches in immunology, cell biology, biochemistry, molecular biology, and computational/systems biology are necessary. Trauma, both accidental and surgical, induces a complex multifaceted response, much of which is the result of the induction of an array of inflammatory and anti-inflammatory mediators (e.g., cytokines, chemokines, and reactive radicals), which in turn regulate biochemical and genetic responses (e.g., autophagy, apoptosis, necroptosis). Similarly, sepsis evokes primitive, highly conserved innate inflammatory pathways which are usually protective, but when excessive, can be detrimental to recovery and survival. These responses ultimately lead to the physiologic changes seen as clinical phenomena (e.g., organ dysfunction). The time has long passed when detailed physiologic monitoring and empiric solutions will suffice. We have entered the era of large-scale genomic, proteomic, and physiomic analysis. It is likely that these approaches, coupled with multi-scale computational analysis as well as the more traditional focused molecular analysis, will be needed to address the complex questions in trauma and sepsis research and guide us to novel therapies. The focus of this proposal is to provide the trainees with the tools to develop relevant hypotheses and then apply state-of-the-art approaches to these questions. Innate immunity, cell signaling, and systems biology have been and remain the areas of focused research in our program.